Liver International最新文献

{"title":"Prothrombin time predicts steroid response in severe alcohol-related hepatitis—Old wine in new bottle","authors":"Mallikarjun Patil","doi":"10.1111/liv.15942","DOIUrl":"10.1111/liv.15942","url":null,"abstract":"","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States","authors":"Gustavo Ayares,&nbsp;Luis Antonio Díaz,&nbsp;Eduardo Fuentes-López,&nbsp;Francisco Idalsoaga,&nbsp;Thomas G. Cotter,&nbsp;Winston Dunn,&nbsp;Douglas Simonetto,&nbsp;Vijay H. Shah,&nbsp;Patrick S. Kamath,&nbsp;Jeffrey V. Lazarus,&nbsp;Ramon Bataller,&nbsp;Marco Arrese,&nbsp;Robert J. Wong,&nbsp;Ashwani K. Singal,&nbsp;Juan Pablo Arab","doi":"10.1111/liv.16023","DOIUrl":"10.1111/liv.16023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1–1.8 and OR: 1.5 95% CI:1.1–2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6–.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73–.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6–.8) along with female Asian population (HR: .40, 95% CI: .26–.62).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic pattern of postprandial bile acids in paediatric non-alcoholic fatty liver disease","authors":"Jiating Huang,&nbsp;Hu Lin,&nbsp;A-Na Liu,&nbsp;Wei Wu,&nbsp;Anna Alisi,&nbsp;Rohit Loomba,&nbsp;Cuifang Xu,&nbsp;Wenqin Xiang,&nbsp;Jie Shao,&nbsp;Guanping Dong,&nbsp;Ming-Hua Zheng,&nbsp;Junfen Fu,&nbsp;Yan Ni","doi":"10.1111/liv.16054","DOIUrl":"10.1111/liv.16054","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Dysregulation of bile acids (BAs), as important signalling molecules in regulating lipid and glucose metabolism, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, static BA profiles during fasting may obscure certain pathogenetic aspects. In this study, we investigate the dynamic alterations of BAs in response to an oral glucose tolerance test (OGTT) among children with NAFLD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We recruited 230 subjects, including children with overweight/obesity, or complicated with NAFLD, and healthy controls. Serum BAs, 7-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19) were quantified during OGTT. Clinical markers related to liver function, lipid metabolism and glucose metabolism were assessed at baseline or during OGTT.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Findings</h3>\u0000 \u0000 <p>Conjugated BAs increased while unconjugated ones decreased after glucose uptake. Most BAs were blunted in response to glucose in NAFLD (<i>p</i> &gt; .05); only glycine and taurine-conjugated chenodeoxycholic acid (CDCA) and cholic acid (CA) were responsive (<i>p</i> &lt; .05). Primary BAs were significantly increased while secondary BAs were decreased in NAFLD. C4 and FGF19 were significantly increased while their ratio FGF19/C4 ratio was decreased in NAFLD. The dynamic pattern of CDCA and taurine-conjugated hyocholic acid (THCA) species was closely correlated with glucose (correlation coefficient <i>r</i> = .175 and −.233, <i>p</i> &lt; .05), insulin (<i>r</i> = .327 and −.236, <i>p</i> &lt; .05) and c-peptide (<i>r</i> = .318 and −.238, <i>p</i> &lt; .05). Among which, CDCA was positively associated with liver fat content in NAFLD (<i>r</i> = .438, <i>p</i> &lt; .05). Additionally, glycochenodeoxycholic acid (GCDCA), CDCA and THCA were potential biomarkers to discriminate paediatric NAFLD from healthy controls and children with obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Interpretation</h3>\u0000 \u0000 <p>This study provides novel insights into the dynamics of BAs during OGTT in paediatric NAFLD. The observed variations in CDCA and HCA species were associated with liver dysfunction, dyslipidaemia and dysglycaemia, highlighting their potential roles as promising diagnostic and therapeutic targets in NAFLD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning uncovers manganese as a key nutrient associated with reduced risk of steatotic liver disease","authors":"Simon Schophaus,&nbsp;Kate Townsend Creasy,&nbsp;Paul-Henry Koop,&nbsp;Jan Clusmann,&nbsp;Julius Jaeger,&nbsp;Varnitha Punnuru,&nbsp;Alexander Koch,&nbsp;Christian Trautwein,&nbsp;Rohit Loomba,&nbsp;Tom Luedde,&nbsp;Kai Markus Schneider,&nbsp;Carolin V. Schneider","doi":"10.1111/liv.16055","DOIUrl":"10.1111/liv.16055","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects approximately 20%–30% of the general population and is linked to high-caloric western style diet. However, there are little data that specific nutrients might help to prevent steatosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed the UK Biobank (ID 71300) 24 h-nutritional assessments and investigated the association between nutrient intake calculated from food questionnaires and hepatic steatosis indicated by imaging or ICD10-coding. The effect of manganese (Mn) on subgroups with risk single nucleotide polymorphism carriage as well as the effect on metabolomics was investigated. All analyses are corrected for age, sex, body mass index, Townsend index for socioeconomic status, kcal, alcohol, protein intake, fat intake, carbohydrate intake, energy from beverages, diabetes, physical activity and for multiple testing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We used a random forest classifier to analyse the feature importance of 63 nutrients and imaging-proven steatosis in a cohort of over 25 000 UK Biobank participants. Increased dietary Mn intake was associated with a lower likelihood of MRI-diagnosed steatosis. Subsequently, we conducted a cohort study in over 200 000 UK Biobank participants to explore the relationship between Mn intake and hepatic or cardiometabolic outcomes and found that higher Mn intake was associated with a lower risk of ICD-10 coded steatosis (OR = .889 [.838–.943], <i>p</i> &lt; .001), independent of other potential confounders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study provides evidence that higher Mn intake may be associated with lower odds of steatosis in a large population-based sample. These findings underline the potential role of Mn in the prevention of steatosis, but further research is needed to confirm these findings and to elucidate the underlying mechanisms.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired HBsAg release and antiproliferative/antioxidant cell regulation by HBeAg-negative patient isolates reflects an evolutionary process","authors":"Michael Basic,&nbsp;Keerthihan Thiyagarajah,&nbsp;Mirco Glitscher,&nbsp;Anja Schollmeier,&nbsp;Qingyan Wu,&nbsp;Esra Görgülü,&nbsp;Pia Lembeck,&nbsp;Jannik Sonnenberg,&nbsp;Julia Dietz,&nbsp;Fabian Finkelmeier,&nbsp;Michael Praktiknjo,&nbsp;Jonel Trebicka,&nbsp;Stefan Zeuzem,&nbsp;Christoph Sarrazin,&nbsp;Eberhard Hildt,&nbsp;Kai-Henrik Peiffer","doi":"10.1111/liv.16048","DOIUrl":"10.1111/liv.16048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The hepatitis B e antigen (HBeAg)-negative infection Phase 3 is characterized by no or minimal signs of hepatic inflammation and the absence of hepatic fibrosis. However, underlying molecular mechanisms leading to this benign phenotype are poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Genotype A, B and D HBeAg-negative patient isolates with precore mutation G1896A from Phase 3 were analysed in comparison with respective HBeAg-positive rescue mutant and HBeAg-positive wild-type reference genomes regarding differences in viral replication, morphogenesis, infectivity and impact on NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE)-dependent gene expression and cellular kinome.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In comparison with reference genomes, the patient isolates are characterized by a lower intra- and extracellular hepatitis B surface antigen (HBsAg)-amount, and HBsAg-retention in the endoplasmic reticulum. Rescue of HBeAg expression increased HBsAg-amount but not its release. Expression of the isolated genomes is associated with a higher Nrf2/ARE-dependent gene expression as compared to reference genomes independent of HBeAg expression. Kinome analyses revealed a decreased activity of receptors involved in regulation of proliferative pathways for all patient isolates compared to the reference genomes. No specific conserved mutations could be found between all genomes from Phase 3.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>HBeAg-negative genomes from Phase 3 exhibit distinct molecular characteristics leading to lower HBsAg synthesis and release, enhanced oxidative stress protection and decreased activity of key kinases, triggering an antiproliferative stage, which might contribute to the lower probability of hepatocellular carcinoma. The observed differences cannot be associated with loss of HBeAg or specific mutations common to all analysed isolates, indicating the phenotype of Phase 3 derived genomes to be the result of a multifactorial process likely reflecting a conserved natural selection process.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “integrin-linked kinase regulates endothelial cell nitric-oxide synthase expression in hepatic sinusoidal endothelial cells”","authors":"","doi":"10.1111/liv.15903","DOIUrl":"10.1111/liv.15903","url":null,"abstract":"<p>Shafiei MS, Lui S, Rockey DC. Integrin-linked kinase regulates endothelial cell nitric-oxide synthase expression in hepatic sinusoidal endothelial cells. Liver Int. 2015 Apr;35(4):1213–1221. PMID: 24906011</p><p>The original version of this article, unfortunately contained a mistake. Since the publication of the article, the authors noticed errors in the beta-actin lanes of Figure 2A,C, and in the total AKT lane in Figure 6B. In the process of figure assembly, original images were inadvertently mislabeled and therefore used incorrectly. The revised figures can be found below. The authors apologize for the errors.</p><p>Figure legend for revised Figure 2.</p><p>Figure legend for revised Figure 6.</p>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.15903","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network meta-analysis of adjuvant chemotherapy in biliary tract cancers: Setting the scene for new randomized evidence","authors":"Francesca Salani,&nbsp;Guglielmo Vetere,&nbsp;Daniele Rossini,&nbsp;Virginia Genovesi,&nbsp;Martina Carullo,&nbsp;Linda Bartalini,&nbsp;Valentina Massa,&nbsp;Laura Bernardini,&nbsp;Miriam Caccese,&nbsp;Silvia Cesario,&nbsp;Jessica Graziani,&nbsp;Giada Grelli,&nbsp;Francesco Mangogna,&nbsp;Caterina Vivaldi,&nbsp;Gianluca Masi,&nbsp;Lorenzo Fornaro","doi":"10.1111/liv.16047","DOIUrl":"10.1111/liv.16047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>The best adjuvant chemotherapy for resected biliary tract cancer (BTC) is under debate, with capecitabine supported by weak evidence. Aim of this network meta-analysis is to estimate the efficacy of different phase II/III regimens, comparing monotherapies (gemcitabine or fluoropyrimidines) head-to-head, against observation and combination regimens.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A comprehensive literature search was conducted on PubMed and EMBASE for phase II/III randomized clinical trials (RCTs) available as of December 2023, reporting hazard ratios (HRs) of overall survival (OS) and event-free survival (EFS). A frequentist framework employing a random-effects model was applied; treatment rankings were outlined according to <i>P</i>-score, based on direct and indirect evidence. Exploratory subgroup analyses for OS were also performed (primary site, resected margin status and nodal involvement).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six RCTs (1979 total patients) were identified. Fluoropyrimidine monotherapy showed significantly better OS (HR .84 [.72–.97]) and EFS (HR .79 [.69–.91]) than observation, as any monotherapy did (HR .84 [.74–.96]; HR .79 [.70–.89]). In the head-to-head comparison for OS, only S1 confirmed to be superior to observation alone (HR .69 [.49–.98]) while fluoropyrimidines achieved the best <i>P</i> score (.81), similarly to any monotherapy (0.92). Combinations failed to prove superior to monotherapies with respect both to OS and EFS. Subgroup analyses were inconclusive due to results' inconsistency and limited sample size.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our work confirmed that adjuvant chemotherapy grants OS and EFS benefit for resected BTC patients. Fluoropyrimidines appeared the most effective option, confirming capecitabine as the preferred choice for the Western population.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of midodrine on HVPG in advanced chronic liver disease and acute-on-chronic liver failure—A pilot study","authors":"Chitranshu Vashishtha,&nbsp;Ankit Bhardwaj,&nbsp;Ankur Jindal,&nbsp;Manoj Kumar,&nbsp;Shiv Kumar Sarin","doi":"10.1111/liv.16033","DOIUrl":"10.1111/liv.16033","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background and Aims</h3>\u0000 \u0000 <p>Nonselective beta-blockers (NSBB) are the mainstay for treatment of portal hypertension (PH), but require caution in decompensated cirrhosis (DC) or acute-on-chronic liver failure (ACLF) with hypotension, hyponatremia, acute kidney injury (AKI) or type 2 hepatorenal syndrome (HRS). Midodrine is oral, rapidly acting, α1-adrenergic agonist. We evaluated acute effects of midodrine on hepatic venous pressure gradient (HVPG) in DC and ACLF with contraindications to NSBB.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Patients of DC (<i>n</i> = 30) with grade III ascites and serum sodium (Na) &lt;130/systolic blood pressure (SBP) &lt;90/type II HRS (group I) and ACLF patients (<i>n</i> = 30) with Na &lt;130/SBP &lt;90/AKI (group II) were included. HVPG was done at baseline and repeated 3 h after 10 mg midodrine. Primary outcome was HVPG response (reduction by &gt;20% or to &lt;12 mmHg).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In group I, midodrine significantly reduced HVPG (19.2 ± 4.6 to 17.8 ± 4.2, <i>p</i> = .02) and heart rate (HR) (86.3 ± 11.6 to 77.9 ± 13.1, <i>p</i> &lt; .01) and increased mean arterial pressure (MAP) (74.1 ± 6.9 to 81.9 ± 6.6 mmHg, <i>p</i> &lt; .01). In group II also, midodrine reduced HVPG (19.1 ± 4.1 to 17.0 ± 4.2) and HR (92.4 ± 13.7 to 84.6 ± 14.1) and increased MAP (85.4 ± 7.3 to 91.2 ± 7.6 mmHg), <i>p</i> &lt; .01 for all. HVPG response was achieved in 3/30 (10%) in group I and 8/30 (26.7%) in group II. On logistic regression analysis, prerenal AKI (OR 11.04, 95% CI 1.83–66.18, <i>p</i> &lt; .01) and increase in MAP (OR 1.22, 95% CI 1.03–1.43, <i>p</i> = .02) were independent predictors of response. Increase in MAP by 8.5 mmHg with midodrine had best cut-off with AUROC of .76 for response.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In decompensated cirrhosis and ACLF patients with contraindications to NSBB, midodrine is useful in decreasing HVPG. Dose of midodrine should be titrated to increase MAP atleast by 8.5 mmHg.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic-specific Pgc-1α ablation drives fibrosis in a MASH model","authors":"Maria Arconzo,&nbsp;Elena Piccinin,&nbsp;Emanuela Pasculli,&nbsp;Marica Cariello,&nbsp;Nicolas Loiseau,&nbsp;Justine Bertrand-Michel,&nbsp;Hervé Guillou,&nbsp;Maria L. Matrella,&nbsp;Gaetano Villani,&nbsp;Antonio Moschetta","doi":"10.1111/liv.16052","DOIUrl":"10.1111/liv.16052","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background &amp; Aims</h3>\u0000 \u0000 <p>Metabolic dysfunction-associated steatohepatitis (MASH) is a growing cause of chronic liver disease, characterized by fat accumulation, inflammation and fibrosis, which development depends on mitochondrial dysfunction and oxidative stress. Highly expressed in the liver during fasting, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) regulates mitochondrial and oxidative metabolism. Given the relevant role of mitochondrial function in MASH, we investigated the relationship between PGC-1α and steatohepatitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We measured the hepatic expression of Pgc-1α in both MASH patients and wild-type mice fed a western diet (WD) inducing steatosis and fibrosis. We then generated a pure C57BL6/J strain loss of function mouse model in which Pgc-1α is selectively deleted in the liver and we fed these mice with a WD supplemented with sugar water that accurately mimics human MASH.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that the hepatic expression of Pgc-1α is strongly reduced in MASH, in both humans and mice. Moreover, the hepatic ablation of Pgc-1α promotes a considerable reduction of the hepatic mitochondrial respiratory capacity, setting up a bioenergetic harmful environment for liver diseases. Indeed, the lack of Pgc-1α decreases mitochondrial function and increases inflammation, fibrosis and oxidative stress in the scenario of MASH. Intriguingly, this profibrotic phenotype is not linked with obesity, insulin resistance and lipid disbalance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In a MASH model the hepatic ablation of Pgc-1α drives fibrosis independently from lipid and glucose metabolism. These results add a novel mechanistic piece to the puzzle of the specific and crucial role of mitochondrial function in MASH development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/liv.16052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing of a suitable protocol for isolating tissue-derived extracellular vesicles and profiling small RNA patterns in hepatocellular carcinoma","authors":"Wenjing Yang,&nbsp;Yu Liu,&nbsp;Jiyan Wang,&nbsp;Te Liu,&nbsp;Tongtong Tian,&nbsp;Tong Li,&nbsp;Lin Ding,&nbsp;Wei Chen,&nbsp;Hao Wang,&nbsp;Jie Zhu,&nbsp;Chunyan Zhang,&nbsp;Baishen Pan,&nbsp;Jian Zhou,&nbsp;Jia Fan,&nbsp;Beili Wang,&nbsp;XinRong Yang,&nbsp;Wei Guo","doi":"10.1111/liv.16011","DOIUrl":"10.1111/liv.16011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Extracellular vesicles (EVs) facilitate cell–cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9⁺ and CD63⁺ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895–1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18101,"journal":{"name":"Liver International","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}